Both posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are prevalent in veterans from the Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) conflicts [1-4], and have been associated with cognitive dysfunction, which may lead to functional impairment and poor community reintegration [1, 2, 5]. PTSD can be highly debilitating not only due to emotional dysregulation, but also due to deficits in the cognitive control processes in areas of complex attention, executive functions and learning [5, 6]. Deficits in these cognitive control functions, important for goal-directed behavior have been linked with difficulties in community reintegration, and educational and occupational functioning in individuals suffering from both PTSD and TBI [7-9]. The combined syndrome of PTSD-mTBI is common, complex, debilitating, and requires special consideration beyond each alone. There is a need for empirically based treatment protocols to address the multiple impairments in returning Veterans with co-morbid PTSD and a history of mild TBI. Goal-Oriented Attentional Self-Regulation (GOALS) is a therapist administered cognitive rehabilitation training that targets executive control functions of applied mindfulness-based attention regulation and goal management, and links them to participant-defined real-life goals [11]. In a prior study with individuals with chronic brain injury [11], this training has improved cognitive performance in areas of complex attention / executive function, memory, complex functional task performance, and daily functioning. Furthermore, functional MRI results after training indicated significantly enhanced modulation of neural processing in extrastriate cortex and changes in prefrontal cortex [12]. Preliminary results from an ongoing study with Veterans with a history of chronic TBI also support improvements post GOALS on neuropsychological measures of attention and executive function, performance on complex 'real-life' tasks, and self-report measures of functional performance. Furthermore, participants also showed improvement on the emotional regulation self-report measures. These findings suggest that improving cognitive control (attentional self- regulation in particular) may also improve functioning in other domains, including emotional regulation and functional performance in daily life. The overall aim of this proposal is to investigate the potential effectiveness of a cognitive training program that targets executive control functions of attentional self-regulation and goal management, Goal-Oriented Attention Self-regulation (GOALS), in Veterans with co-morbid PTSD - mTBI and cognitive difficulties. In a randomized, controlled intervention study design, 54 OIF/OEF/OND Veterans with a diagnosis of PTSD, history of mTBI and residual cognitive difficulties will participate in experimental (GOALS), and/or active comparison (Brain Health Education - EDU) interventions matched for time and intensity. Participants will be randomized to start with either 5 weeks of GOALS or EDU training. Those who begin with EDU will cross-over to GOALS, while those begin with GOALS will have 5 weeks of self-driven practice only. Both groups will participate in pre and post intervention measurements at baseline, weeks 5 and 10. Long-term follow-up will be at 6 months. Pre- and post-intervention measurements will include performance on untrained: neuro-cognitive tests assessing targeted and non-targeted cognitive domains, complex functional task performance in low structure 'real-world' setting, and self-report measures of daily functioning and emotional regulation/heath. When completed, these studies will inform us whether a functional approach, training core attentional self- regulatory control functions, via personally-relevant activities, will be effective in improving functioning for individuals with PTSD and mTBI. The study design will provide a test not only of potential benefits on real life functioning, but also determine to what extent the benefits are related to actual changes in hypothetically targeted cognitive and emotional functions. PUBLIC HEALTH RELEVANCE: One of the most pressing concerns within the VA currently is the provision of interventions that address the cognitive as well as emotional problems faced by veterans with concurrent mild TBI and PTSD. When completed, these studies will inform us whether a functional approach, training core attentional self-regulatory control functions via personally-relevant activities, wil be effective in improving functioning for individuals with PTSD and mild TBI. The study design will provide a test not only of potential benefits on real life functioning, but also determine to what extent these benefits are related to actual changes in hypothetically targeted cognitive and emotional functions. These studies will provide a foundation for future studies to investigate the neural mechanisms that support improvements in these functions.